Dicycloplatin: Assessing the efficacy of a novel platinum analog for treatment of urothelial carcinoma of the bladder

• Published in: Journal of clinical oncology Vol. 42; no. 4_suppl; p. 689
• Main Authors: Zekan, David, Jackson, Barbara, Hogan, Thomas F., Kandzari, Stanley
• Format: Journal Article
• Language: English
• Published: 01.02.2024
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2024.42.4_suppl.689

689 Background: Platinum-based chemotherapies are a component of standard-of-care regimens for urothelial carcinoma (UC). These nephrotoxic drugs are often dose-limiting, with cisplatin and carboplatin most used. Dicycloplatin (DCP) has better solubility and stability, with comparable efficacy and better tolerability. Some suggest use of DCP as primary treatment for non-muscle-invasive bladder cancer. We exposed UC cell lines to DCP in vitro to assess efficacy. Methods: A high grade (IV) in vitro UC cell line (TCCSUP) was exposed to varying concentrations of cisplatin (0-600 ug/mL), carboplatin (0-600 ug/mL), oxaliplatin (0-4.0 ug/mL), and DCP (0-350 ug/mL). Grade II-IV cells were exposed to concentrations of DCP (0-350 ug/mL) to assess time- and concentration-dependence of growth inhibition, and intravesical simulation. Growth inhibition was determined following exposures of 24, 48, and 72 hours using exposure to a tetrazolium dye assessing mitochondrial dehydrogenase activity. Results: DCP, cisplatin, and carboplatin effectively achieved >90% cell-kill at 72 hours. Concentrations of 325 ug/mL DCP, 50 ug/mL cisplatin, and 600 ug/mL carboplatin are sufficient for >90% cell-kill, with cisplatin boasting highest kills at lowest concentration/time intervals. Dose- and time-dependent cell-kill were demonstrated at varying concentrations of DCP in grade II-IV cell lines, including cells exposed in a intravesical fashion. Conclusions: DCP has in vitro cell-kill efficacy in a time- and concentration-dependent manner in grade II-IV UC cell lines, showing promise for its IV, PO, and intravesical use for UC of the bladder in the primary and adjuvant/neoadjuvant setting. Animal studies are forthcoming to assess in vivo efficacy prior to proceeding with clinical trials.